Aim: Ablation of auto-reactive immune cells followed by autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of multiple sclerosis (MS) has been explored for the previous two decades. Morbidity and mortality rates originally limited referral for AHSCT in auto-immune disease but a reduction in treatment toxicity has facilitated increased clinical trials in the field. Here we present the outcomes of patients withadvanced, treatment refractory MS undergoing AHSCT in a Phase II study at our institute. We evaluate the safety and efficacy of AHSCT with intermediate-intensity immunosuppression in patients with highly aggressive MS.

Methods: A single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS) commenced at St Vincent's Hospital in December 2010. Patients eligible for AHSCT had an Expanded Disability Status Scale (EDSS) of 2.0-7, had failed two prior disease-modifying therapies and displayed evidence of ongoing disease activity manifesting as clinical relapses and/or new MRI lesions in the year prior to AHSCT. CD34+ mobilisation with cyclophosphamide and G-CSF was performed, followed by conditioning with a BEAM (carmustine, etoposide, cytarabine, melphalan) + ATG (antithymocyte globulin) chemotherapeutic regimen. Patients underwent clinical assessment and peripheral blood collection for tissue banking at 3, 6, 12 months and yearly to 5 years. Gadolinium enhanced MRI was performed at 6, 12 months and yearly to 5 years. The primary outcomes were event-free survival and overall survival. Event free survival (EFS) was defined as no clinical or radiological relapses and no evidence of disability progression (by EDSS). Polychromic multi-parameter flow cytometry was performed for evaluation of post-transplant immune reconstitution.

Progression-free survival, clinical relapse-free survival (RFS), and MRI activity-free survival for the cohort were 80%, 90% and 95% respectively. Event free survival in the RRMS cohort was 90%. Sustained improvement in neurologic function by EDSS was seen in 15/40 (37.5%) of patients; 11 (42.3%) RRMS patients and 4 (28.6%) SPMS patients. MS quality of life score (MSQOL) - physical improved by 14.4 points (p=0.004) and MSQOL - mental improved by 10.3 points (p=0.08). Treatment related mortality was 0%. Adverse effects due to AHSCT were consistent with expected toxicities. One patient required admission to the intensive care unit in the post-transplant period due to serum sickness. There were no significant late neurologic adverse effects noted and no recorded cases of progressive multifocal leukoencephalopathy noted.